Kinetic Modeling of [<sup>11</sup>C]Raclopride: Combined PET-Microdialysis Studies

DOI Web Site Web Site 被引用文献7件
  • Christopher J. Endres
    Positron Emission Tomography Department, Clinical Center, National Institutes of Health, Bethesda, Maryland, U.S.A.
  • Bhaskar S. Kolachana
    Clinical Brain Disorders Branch, Bethesda, Maryland, U.S.A.
  • Richard C. Saunders
    Clinical Brain Disorders Branch, Bethesda, Maryland, U.S.A.
  • Tom Su
    Experimental Therapeutics Branch, National Institutes of Mental Health, Bethesda, Maryland, U.S.A.
  • Daniel Weinberger
    Clinical Brain Disorders Branch, Bethesda, Maryland, U.S.A.
  • Alan Breier
    Experimental Therapeutics Branch, National Institutes of Mental Health, Bethesda, Maryland, U.S.A.
  • William C. Eckelman
    Positron Emission Tomography Department, Clinical Center, National Institutes of Health, Bethesda, Maryland, U.S.A.
  • Richard E. Carson
    Positron Emission Tomography Department, Clinical Center, National Institutes of Health, Bethesda, Maryland, U.S.A.

抄録

<jats:p>The in vivo binding of D<jats:sub>2</jats:sub>receptor ligands can be affected by agents that alter the concentration of endogenous dopamine. To define a more explicit relation between dopamine and D<jats:sub>2</jats:sub>receptor binding, the conventional compartment model for reversible ligands has been extended to account for a time-varying dopamine pulse. This model was tested with [<jats:sup>11</jats:sup>C]raclopride positron emission tomography and dopamine microdialysis data that were acquired simultaneously in rhesus monkeys. The microdialysis data were incorporated into the model assuming a proportional relation to synaptic dopamine. Positron emission tomography studies used a bolus-plus-infusion tracer delivery with amphetamine given at 40 minutes to induce dopamine release. The extended model described the entire striatal time–activity curve, including the decrease in radioactivity concentration after an amphetamine-induced dopamine pulse. Based on these results, simulation studies were performed using the extended model. The simulation studies showed that the percent decrease in specific binding after amphetamine measured with the bolus-plus-infusion protocol correlates well with the integral of the postamphetamine dopamine pulse. This suggests that changes in specific binding observed in studies in humans can be interpreted as being linearly proportional to the integral of the amphetamine-induced dopamine pulse.</jats:p>

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